rs768207

Positions:

• chr18-52352600-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005215.4(DCC):​c.91+11722C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,156 control chromosomes in the GnomAD database, including 2,544 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (2544 hom., cov: 32)
• Consequence: DCC NM_005215.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.752

Genes affected

DCC (HGNC:2701): (DCC netrin 1 receptor) This gene encodes a netrin 1 receptor. The transmembrane protein is a member of the immunoglobulin superfamily of cell adhesion molecules, and mediates axon guidance of neuronal growth cones towards sources of netrin 1 ligand. The cytoplasmic tail interacts with the tyrosine kinases Src and focal adhesion kinase (FAK, also known as PTK2) to mediate axon attraction. The protein partially localizes to lipid rafts, and induces apoptosis in the absence of ligand. The protein functions as a tumor suppressor, and is frequently mutated or downregulated in colorectal cancer and esophageal carcinoma. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCC	NM_005215.4	c.91+11722C>A		intron_variant		ENST00000442544.7
DCC	XM_017025568.2	c.91+11722C>A		intron_variant
DCC	XM_017025569.2	c.91+11722C>A		intron_variant
DCC	XM_047437311.1	c.91+11722C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCC	ENST00000442544.7	c.91+11722C>A		intron_variant		1	NM_005215.4	P1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27450 AN: 152038 Hom.: 2535 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.174

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.181 AC: 27470 AN: 152156 Hom.: 2544 Cov.: 32 AF XY: 0.184 AC XY: 13672 AN XY: 74372

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.178

Alfa AF: 0.185 Hom.: 565

Bravo AF: 0.183

Asia WGS AF: 0.242 AC: 839 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.053
DANN	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs768207; hg19: chr18-49878970;